Norfloxacin Therapy for Hepatopulmonary Syndrome: A Pilot Randomized Controlled Trial

BACKGROUND & AIMS: The hepatopulmonary syndrome occurs in up to one-third of patients with cirrhosis. Animal models of this disease suggest that endotoxemia might cause nitric oxide-mediated vascular dilatation that can be inhibited by the antibiotic norfloxacin. We sought to test this hypothesis in humans. METHODS: We conducted a pilot randomized, controlled crossover trial of norfloxacin 400 mg twice daily for 4 weeks with a 4-week washout period to assess the feasibility of a larger trial. The primary clinical end point was change in alveolar-arterial oxygen gradient (AaDO(2)). RESULTS: Recruitment was challenging, and change in AaDO(2) was highly variable. We recruited 9 adults (1 woman; age, 60 +/- 9 years; AaDO(2), 50 +/- 22 mm Hg). AaDO(2) decreased by 0.8 +/- 4.8 and 3.4 +/- 12.4 mm Hg while on norfloxacin and placebo, respectively (P = .59). CONCLUSIONS: Recruitment difficulties and variability of the primary outcome measure suggest the need for a multicenter clinical research network for future therapeutic trials in this disease. There was no major effect of norfloxacin on gas exchange in patients with hepatopulmonary syndrome.